Monocyte/macrophages (m/m) initiate an immune response by presenting antigens in the form of peptides to T and B lymphocytes. It is generally recognized that physical interaction of the various subpopulations is necessary for induction of the immune response cascade. In vivo and in vitro, two of the cell populations that are involved in these events are m/m and CD4+ lymphocytes, the primary targets of HIV infection. Studies were undertaken to investigate the alteration of the normal regulatory pathways of the immune response by HIV-1 infection. Peripheral blood T lymphocytes and m/m were isolated from noninfected individuals and the m/m infected with HIV-1. Antibodies reacting with cell surface markers known to participate in m/m-T-cell interaction were added to cultures and assessed for their ability to inhibit T-cell response and infection. Preliminary results indicate that the structures involved in m/m-T-cell interaction are also involved in cell-to-cell transfer of HIV-1. The presence of cell surface structures on the HIV-1 virus was determined using concentrated disrupted virus, high pressure liquid chromatography separation of the various components, and amino acid sequencing of the products. HLA-DR A and B chains as well as beta-2 microglobulin were found in molar quantities comparable to that of several of the viral pro- teins. The functional relevance of these molecules on the surface of the HIV-1 virus and HIV-1 pathogenesis are under investigation. A flow cytometric based assay that detects immunoglobulin class and subclass antibodies to HIV-1 protein was developed and applied to identify antibody isotype response in sera from mothers giving birth to HIV-1-infected and noninfected offspring.